- Associated Press - Wednesday, January 22, 2014

PHILADELPHIA (AP) - A shriveled piece of intestine is all that remains of the unfortunate soul who died in Philadelphia’s 1849 outbreak of cholera. Researchers do not even know his name.

Yet after sophisticated computer analysis, the patient’s yellowish tissue has yielded a wealth of information: the DNA of his killer.

The genome of this cholera strain, which claimed more than 1,000 lives, was described in a new study in the New England Journal of Medicine.

The findings will be of no immediate help to doctors who treat the modern form of the disease, a waterborne illness that still plagues developing countries with inadequate sanitation. The results, however, show the 19th-century Philadelphia strain of bacteria was not so different from its modern cousin, offering clues as to how the microbe has tweaked itself to remain a deadly fixture in the human experience.

The lab that did the analysis, at McMaster University in Ontario, is well-known for extracting DNA from fossils many thousands of years old, such as woolly mammoth bones.

The team, led by geneticist Hendrik Poinar, was not so sure about finding cholera from less than 200 years ago.

The microbe, formally called Vibrio cholerae, infects only the intestines, causing severe diarrhea, and does not show up in a victim’s bones. So unless someone had made a point of storing some of the soft tissue in a jar, the scientists were out of luck.

Care to guess who had something like that sitting on a shelf?

Right the first time. The Mütter Museum of the College of Physicians of Philadelphia has at least six intestines from cholera victims in 1849.

“Our wet specimens are very well inventoried,” said curator Anna Dhody, a coauthor of the DNA study. “We know pretty much exactly what we have and where it is.”

Still unclear was whether the bacterial DNA would be too degraded to decipher, but the situation was promising, Dhody said. The tissue was preserved in alcohol, and the bottles appeared to have been unopened since 1849. Most were sealed off with an elaborate four-layer covering: a lead disk, a piece of pig’s bladder, a scrap of parchmentlike material, and finally a coating of black pitch.

The researchers used scalpels to extract six tissue bits the size of postage stamps - a procedure museum officials allowed after deciding it could yield valuable information.

The team was indeed able to recover cholera DNA from one sample - though it was highly fragmented, its average length fewer than 50 base pairs, said lead author Alison Devault, a Ph.D. candidate in McMaster’s anthropology department. To put that in perspective, V. cholerae’s entire genome measures about four million base pairs, while the human genome is three billion pairs.

The scientists used a series of chemical and computer techniques to fish out fragments that appeared to be from the 1849 bacteria, matching them as best they could to the framework of a known cholera genome from the mid-20th century.

The patient’s intestine contained fragments from the DNA of multiple cholera-causing cells, so the scientists had multiple copies of each fragment - a good thing, for many were damaged. By looking at many versions of each fragment, they could guard against errors - almost like looking at multiple damaged versions of the same jigsaw puzzle.

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